Chlamydial Immunity and Vaccine Development

Caldwell, Harlan D.

Abstract

Chlamydia trachomatis serovars A-L3 are the causative agents of hyperendemic blinding trachoma, a largely neglected disease of the developing world, and sexually transmitted infections (STI) that are epidemic world wide. Control of these important human diseases is the long term goal of this project. Towards this end our goal is to develop a safe and efficacious vaccine to prevent these diseases. The obligate intracellular life style, complex developmental biology, and antigenic structure of chlamydiae have severally hindered progress in vaccine development. A major hurdle in chlamydial vaccine development has been the unavailability of antigens capable of providing broadly reactive protective immunity against the multiple serovariants (15) that cause oculogenital infections. The immediate goal of this work was to discover antigen(s) with characteristics amenable for the development of a broad based multi-strain vaccine against chlamydial infections and to test the candidates in pre-clinical models of infection and disease.

Funding Agency

• Agency: National Institute of Health (NIH)
• Institute: National Institute of Allergy and Infectious Diseases (NIAID)
• Type: Intramural Research (Z01)
• Project #: 1Z01AI000672-16
• Application #: 7732497
• Support Year: 16
• Fiscal Year: 2008
• Total Cost: $687,147

Institution

• Name: National Institute of Allergy and Infectious Diseases
• Country: United States

Publications

Brown, Deborah M; Lee, Sarah; Garcia-Hernandez, Maria de la Luz et al. (2012) Multifunctional CD4 cells expressing gamma interferon and perforin mediate protection against lethal influenza virus infection. J Virol 86:6792-803

Brown, Deborah M (2010) Cytolytic CD4 cells: Direct mediators in infectious disease and malignancy. Cell Immunol 262:89-95

Swanson, Kena A; Taylor, Lacey D; Frank, Shaun D et al. (2009) Chlamydia trachomatis polymorphic membrane protein D is an oligomeric autotransporter with a higher-order structure. Infect Immun 77:508-16

Brown, Deborah M; Kamperschroer, Cris; Dilzer, Allison M et al. (2009) IL-2 and antigen dose differentially regulate perforin- and FasL-mediated cytolytic activity in antigen specific CD4+ T cells. Cell Immunol 257:69-79

Carlson, John H; Whitmire, William M; Crane, Deborah D et al. (2008) The Chlamydia trachomatis plasmid is a transcriptional regulator of chromosomal genes and a virulence factor. Infect Immun 76:2273-83

Kari, Laszlo; Whitmire, William M; Carlson, John H et al. (2008) Pathogenic diversity among Chlamydia trachomatis ocular strains in nonhuman primates is affected by subtle genomic variations. J Infect Dis 197:449-56

Nelson, David E; Taylor, Lacey D; Shannon, Jeffrey G et al. (2007) Phenotypic rescue of Chlamydia trachomatis growth in IFN-gamma treated mouse cells by irradiated Chlamydia muridarum. Cell Microbiol 9:2289-98

McClarty, Grant; Caldwell, Harlan D; Nelson, David E (2007) Chlamydial interferon gamma immune evasion influences infection tropism. Curr Opin Microbiol 10:47-51

Carlson, John H; Wood, Heidi; Roshick, Christine et al. (2006) In vivo and in vitro studies of Chlamydia trachomatis TrpR:DNA interactions. Mol Microbiol 59:1678-91

Nelson, David E; Crane, Deborah D; Taylor, Lacey D et al. (2006) Inhibition of chlamydiae by primary alcohols correlates with the strain-specific complement of plasticity zone phospholipase D genes. Infect Immun 74:73-80